Exploring the Distinct Regulatory Actions and Molecular Pathways of Coptisine Through Network Pharmacology: Insights...

To investigate the potential targets and underlying mechanisms of coptisine in regulating platelet activation and thrombosis by integrating an approach combining network pharmacology and experimental validation. An in vivo carotid artery thrombosis model induced by FeCl₃-mediated endothelial injury was established in mice to evaluate the antithrombotic effects of coptisine. A combination of network pharmacology prediction and both in vivo and in vitro experimental validation was employed to elucidate the antithrombotic mechanisms of coptisine. Molecular docking simulations were performed using AutoDock Vina to assess the binding interactions between coptisine and its targets. The in vitro antiplatelet effects of coptisine were assessed using platelet aggregation assays induced by thrombin, ADP, and collagen, as well as a thrombin-induced platelet activation model. Administration of coptisine significantly reduced thrombus formation in the mouse model of carotid artery thrombosis. Network pharmacology analysis identified four key genes-NFKB1, PTGS2, STAT1, and ACE-as potential core targets contributing to the antithrombotic effects of coptisine. Functional enrichment analysis further indicated the involvement of these targets in pathways relevant to thrombosis and inflammation. Molecular docking studies demonstrated strong binding affinities between coptisine and the identified targets. Both in vivo and in vitro studies confirmed that coptisine treatment markedly attenuated thrombin-induced platelet activation, as evidenced by reduced platelet inflammation and decreased levels of platelet granule release. This study demonstrates that coptisine exerts significant protective effects against thrombosis-related diseases through modulation of the NF-κB and MAPK signaling pathways.